This is a renewal of a Program Project on the molecular basis of biological recognition and assembly. As before, the main goal of the Program Project is to bring together and strengthen the collaboration between six structural molecular biologists, in order to study problems in the structure, recognition, and assembly of biological macromolecules and complexes. Physical techniques used include x-ray crystallography of proteins and nucleic acids, electron microscopy and image reconstruction, and one and two-dimensional nuclear magnetic resonance. Specific goals to be proposed include: (a) X-ray and nmr examination of synthetic DNA molecules, and their complexes with antitumor drugs and proteins. (b) Design of more efficient DNA sequence-specific antitumor drugs, as vectors capable of differentiating beween neoplastic and normal cells, or between invader and host cells. (c) X-ray analysis of the multi-subunit allosteric enzymes ribulose bisphosphate carboxylase and glutamine synthetase. Investigation of the relative roles of hydrophobic, electrostatic and hydrogen-bonding interactions in protein stabilization and assembly, (d) X-ray analysis of three electron transfer proteins and complexes: Azotobacter nitrogenase iron protein, a flavodoxin/cytochrome c complex, and the R. sphaeroides photosynthetic reaction center complex. (e) Analysis of ribosome structure by electro microscopy and image reconstruction, including use of immunochemical and DNA hybridization probes. (f) Study of factors controlling the self assembly of bacteriophage T4 tails and heads, using genetics, electron microscopy, in vitro reconstructions and protein sequence information. (g) Maintenance and upgrading of a communal x-ray data collecting facility, including rotating anode generators, automatic diffractometer, and multiwire area detector. (h) Maintenance of electron microscope facilities for research and training purposes. (i) Establishment of an nmr facility for macromolecular studies, built around a 500 MegaHertz nmr spectrometer.